Fri Sep 30 2022

97 articles - From Friday Sep 23 2022 to Friday Sep 30 2022

parm_toc.knit

Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…

J Hematol Oncol

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China.

Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy.

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Meta-analysis

meta-analyses and systematic reviews

Haematologica

Comment on: Antibody response after vaccination against SARS-CoV-2 in adults with haematological malignancies: a systematic review and meta-analysis.

Not available.

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Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

lovo-cel gene therapy for Sickle Cell Disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study.

(ClinicalTrials. gov: NCT02140554; Trial: HGB-206.)

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Romiplostim use in pregnant women with immune thrombocytopenia.

Seven of 12 infants with neonatal thrombocytopenia had resolution of thrombocytopenia before discharge; al 12 were discharged. Review of pregnancies in women exposed to romiplostim did not reveal any specific safety concerns for mothers, fetuses, or infants.

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Blood

A MIR17HG-derived Long Noncoding RNA Provides an Essential Chromatin Scaffold for Protein Interaction and Myeloma Growth.

Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent anti-tumor effects both in vitro and in vivo in three pre-clinical animal models, including a clinically relevant PDX-NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.

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Allogeneic stem cell transplantation compared to conservative management in adults with inborn errors of immunity.

Sensitivity analyses removing patients with CVID and their matched transplanted patients confirm these results. AlloSCT prevents progressive morbidity associated with IEI in adults, which may outweigh the negative impact of TRM.

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An Open-Label, Single-Arm, Phase 2 Trial of Valemetostat in Relapsed or Refractory Adult T-Cell Leukemia/Lymphoma.

Grade =3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL.

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Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from EPICOVIDEHA survey.

Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals. EPICOVIDEHA ( National Clinical Trials identifier NCT04733729) is an international open web-based registry for patients with HMs infected with SARS-CoV-2.

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Efficacy of JAK 1/2 inhibition in murine immune bone marrow failure.

RUX only modestly suppressed lymphoid and erythroid hematopoiesis in normal and irradiated CByB6F1 mice. Our data supports clinical trials of JAK/STAT inhibitors in human AA and other immune bone marrow failure syndromes.

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Genomic Profiling for Clinical Decision Making in Myeloid Neoplasms and Acute Leukemia.

The 2022 International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias makes extensive use of genomic data. This report aims to help physicians and laboratorians implement genomic testing for diagnosis, risk stratification, and clinical decision making and illustrates the potential of genomic profiling for enabling personalized medicine in patients with these hematologic neoplasms.

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MRD dynamics during maintenance for improved prognostication of 1280 myeloma patients in TOURMALINE-MM3 and -MM4 trials.

We demonstrate the limited prognostic value of a single timepoint MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD- status as a relevant endpoint during maintenance and confirm the increased progression risk in patients converting to MRD+ from MRD- status.

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Blood Adv

Dabigatran in the treatment and secondary prophylaxis of venous thromboembolism in children with thrombophilia.

Safety profiles were consistent with those reported previously. Although they should be interpreted with caution, these exploratory findings suggest dabigatran could be an appropriate long-term anticoagulant for children with thrombophilia.

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Enasidenib as Maintenance following Allogeneic Hematopoietic Cell Transplantation for IDH2-Mutated Myeloid Malignancies.

The study was registered at ClinicalTrials. gov (NCT03515512).

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Genetically determining individualized clinical reference ranges for the biomarker tryptase can limit unnecessary procedures and unmask myeloid neoplasms.

Moreover, substantial BST elevations (e. g., >100 ng/mL) which would ordinarily prompt bone marrow biopsy, can result from TPSAB1 replications alone and thus be within 'normal' limits for certain individuals with HaT.

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Haplotype sequence collection of ABO blood group alleles by long-read sequencing reveals putative A1-diagnostic variants.

Overall, our sequencing strategy proved powerful for producing high-quality ABO haplotypes and holds promise for generating similar collections for other blood groups. The publicly available collection of 154 haplotypes will serve as a valuable resource for molecular analyses of ABO, as well as studies about function and evolutionary history of ABO.

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Health-related quality of life with lisocabtagene maraleucel vs standard of care in relapsed or refractory LBCL.

This study is registered at clinicaltrials. gov as #NCT0357531.

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Hodgkin lymphoma and female fertility: a multicenter study in women treated with ABVD.

The number of pregnancies, births and the time to start a pregnancy in young women treated with ABVD for HL is not different to that of controls. Therefore, female with HL and treated by ABVD should be reassured in regards to fertility.

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Increasing tissue requirements in lymphoma trials may exclude patients with high risk disease or worse prognosis.

Thus, patients who undergo CNB have poor risk features, have inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses and might not be able to meet tissue requirements of biomarker-driven clinical trials. Thus, increasing tissue requirements of biomarker driven clinical trials may result in exclusion of high risk DLBCL pts who need novel agents.

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Novel antimyeloma therapeutic option with inhibition of the HDAC1-IRF4 axis and PIM kinase.

Class I HDAC and PIM kinase inhibitors cooperatively suppressed MM cell growth in the presence of IL-6 and in vivo. Therefore, the present results demonstrate the potential of the simultaneous targeting of the intrinsic HDAC1-IRF4 axis plus externally activated PIM2 as an efficient therapeutic option for MM fostered in bone marrow.

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Patient perspectives on testing for clonal hematopoiesis of indeterminate potential.

Our findings highlight the importance of effective risk communication and adequate psychosocial support when considering biomarkers of future risks in cancer survivors. This trial is registered at as NCT01468246.

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Production and nonclinical evaluation of an autologous iPSC-derived platelet product for the iPLAT1 clinical trial.

This report displays a complete system for the GMP-based production of iPSC-PLTs and the required non-clinical studies, and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs, in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products which use iPSC-derived progenitor cells as an MCB.

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RNA-Regulatory Exosome Complex Suppresses an Apoptotic Program to Confer Erythroid Progenitor Cell Survival In Vivo.

RNA-seq analysis of Exosc3-ablated BFU-E revealed elevated transcripts encoding multiple pro-apoptotic factors, and the mutant erythroid progenitors exhibited increased apoptosis. We propose that the EC controls an ensemble of apoptosis-regulatory RNAs, thereby promoting erythroid progenitor survival and developmental erythropoiesis in vivo.

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The Prevalence of Thrombocytopenia in Patients with Acute Cancer-Associated Thrombosis.

Concurrent diagnoses of CAT and thrombocytopenia are very common, especially among patients with hematologic malignancies.

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U2AF1 and EZH2 mutations are associated with nonimmune hemolytic anemia in myelodysplastic syndromes.

Somatic mutations encoding splicing factors may affect erythrocyte membrane components, biochemical properties, and RBC metabolic function, which underpin the development of atypical clones from erythroid precursors in MDS presenting with hemolysis. Future studies will explore the contribution of altered splicing to the development of acquired hemoglobinopathies.

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Blood Cancer J

Comparison of outcomes for HLA-matched sibling and haplo-identical donors in Myelodysplastic syndromes: report from the chronic malignancies working party of EBMT.

This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it's use when no better donor is available.

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Haematologica

Contribution of measurable residual disease status to prediction accuracy of relapse and survival in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation.

Not available.

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Donor cell-derived myelofibrosis relapse after allogeneic stem cell transplantation.

Not available.

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Genome-wide CRISPR screens identify ferroptosis as a novel therapeutic vulnerability in acute lymphoblastic leukemia.

Detailed molecular analysis of B-ALL cells suggest that they are primed to undergo ferroptosis as they exhibit high steady-state oxidative stress potential, a low buffering capacity, and a disabled GPX4-independent secondary lipid peroxidation detoxification pathway. Finally, we validated the sensitivity of B-ALL to ferroptosis induction using patient-derived B-ALL samples.

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Heterogeneity in long term outcomes for R-ISS stage II in newly diagnosed multiple myeloma patients.

In conclusion, stratification of patients in the R-ISS stage II group can be improved by taking into account CA and ISS. However, this does not improve predictive performance of survival models.

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One disease, many faces.

Not available.

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Plasminogen activator-coated nanobubbles targeting cell-bound ß2-glycoprotein I as a novel thrombus-specific thrombolytic strategy.

Finally, treatment of C3-gain-of-function mice with rtPA-tNBs, that target ß2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NBs. Our findings suggest that targeting cell-bound ß2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APSunrelated thrombotic conditions.

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Reply to Shao and Zhou.

Not available.

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Rituximab therapy after pediatric hematopoietic stem cell transplantation can cause prolonged B cell impairment and increases the risk for infections - a retrospective matched cohort study.

Not available.

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Small molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy.

Specifically, SUMOi increased the number of memory B-cells as well as cytotoxic and memory T-cells, subsets that are attributed a key role within a coordinated antitumor immune response. In summary, our data constitute pharmacologic SUMOi as a powerful therapy in a subset of B-cell lymphomas causing massive remodeling of the normal B-cell and T-cell compartment.

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Von Willebrand factor in the plasma and in the tumor tissue predicts cancerassociated thrombosis and mortality.

Not available.

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Leukemia

A primary hierarchically organized patient-derived model enables in depth interrogation of stemness driven by the coding and non-coding genome.

A novel non-coding regulatory element was identified with a new computational approach using functionally validated primary AML LSC fractions and its role in LSC stemness validated through efficient CRISPR editing using methods optimized for OCI-AML22 LSC. Collectively, OCI-AML22 constitutes a valuable resource to uncover mechanisms governing CSC driven malignancies.

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Characteristics of anti-CLL1 based CAR-T therapy for children with relapsed or refractory acute myeloid leukemia: the multi-center efficacy and safety interim analysis.

4 out of 8 patients achieved morphologic leukemia-free state (MLFS) and minimal residual disease (MRD) negativity, 1 patient with MLFS and MRD positivity, 1 patient achieved complete remission with incomplete hematologic recovery (CRi) but MRD positivity, 1 patient with partial remission (PR), and 1 patient remained at stable disease (SD) status but had CLL1-positive AML blast clearance. These results suggested that anti-CLL1-based CAR-T cell immunotherapy can be considered as a well-tolerated and effective option for treating children with R/R-AML.

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Compartment-specific mutational landscape of clonal hematopoiesis.

Patients with overt myeloid malignancies showed higher mutation numbers and allele frequencies and a shifting mutation landscape, notably characterized by increasing prevalence of DNMT3A codon R882 variants. Collectively, our data provide novel insights into the genetics, evolution, and spatial and lineage-specific BM involvement of CH.

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Impact of conditioning chemotherapy on lymphocyte kinetics and outcomes in LBCL patients treated with CAR T-cell therapy.

The impact of CCT on lymphocyte count is affected by use of bridging therapy but change in lymphocyte count is independently associated with efficacy. Studies aimed at investigating macrophage biology in this setting may suggest strategies to increase the efficacy of CCT and improve outcomes.

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Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance.

Gene expression analysis revealed enriched stemness and decreased myeloid lineage differentiation in spleen leukemic stem and progenitor cells (LSPCs). These results demonstrate that splenic RPM form a niche that maintains CML LSCs in a quiescent state, resulting in disease progression and resistance to therapy.

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Thromb Haemost

Carotid Stenosis and Stroke: Medicines, Stents, Surgery - "Wait-and-See" or Protect?

no abstract.

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Dual specificity tyrosine phosphorylation regulated kinase 1B inhibition promotes megakaryocyte polyploidization and platelet production.

In summary, DYRK1B plays an important role in megakaryocyte maturation and platelet production by interacting with cyclin D1 and P27. DYRK1B inhibition has potential therapeutic value in transient thrombocytopenia treatment.

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Factor XII explored with AlphaFold - opportunities for selective drug development.

Not applicable.

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Hyperhomocysteinemia in cardiovascular diseases: revisiting observational studies and clinical trials.

Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for vitamin B deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the lowering homocysteine effect according to hyperhomocysteinemia categories at baseline.

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Inflammatory markers differentiate cerebral venous sinus thrombosis from mimics.

In conclusion, inflammatory markers in CVST were different from those in mimics. These markers, especially IL-6, could not only differentiate CVST from its mimics, but also evaluate CVST severity and prognosis.

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TEMPORARY REMOVAL: Direct oral anticoagulants in antithrombin deficiency: initial experience in a single center.

If you have any questions, please contact am-query@thieme. com.

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Uric Acid induces a pro-atherothrombotic phenotype in human endothelial cells by imbalancing TF/TFPI pathway.

The present in vitro study, shows that one of the mechanisms by which high levels of UA contributes to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a non-physiological, pro-thrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

Somatic variation in normal tissues: friend or foe of cancer early detection?

Somatic variation and the factors governing homeostasis of normal tissues should be taken into account when devising strategies for cancer prevention and early detection.

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Blood

Do you need the immune system to cure ALL?

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Endothelial cell-mediated venous thrombosis.

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GVHD: pDCs providing VIP protection.

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How thinly can one slice the AML diagnostic pie?

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iTPP: nature vs nurture?

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Lost in translation: cytoplasmic UBA1 and VEXAS syndrome.

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Predicting the future in MCL with MRD.

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Raise the roof, build the floor.

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CA Cancer J Clin

Prevention of device-related infections in patients with cancer: Current practice and future horizons.

The authors present many general principles for the prevention of these infections followed by specific device-related recommendations in a systematic manner. The continuous involvement and meaningful cooperation between regulatory entities, industry, specialty medical societies, hospitals, and infection control-targeted interventions, along with primary care and consulting health care providers, are al vital for the sustained reduction in the incidence of these preventable infections.

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Lancet Haematol

Access to and affordability of CAR T-cell therapy in multiple myeloma: an EBMT position paper.

Here, we identify two important issues: affordability and access to CAR T-cell treatment. This consensus statement from clinical investigators, clinicians, nurses, and patients from the European Society for Blood and Marrow Transplantation (EBMT) proposes solutions as part of an innovative collaborative strategy to make CAR T-cell therapy accessible to al patients with multiple myeloma.

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Caregivers-an undervalued and underused essential.

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Faecal microbiota transplantation in patients with haematological malignancies undergoing cellular therapies: from translational research to routine clinical practice.

Therefore, faecal microbiota transplantation has been evaluated in patients with haematological malignancies for various indications, including Clostridioides difficile infection, eradication of multidrug-resistant bacteria, and steroid refractory acute GVHD. In addition, use of prophylactic faecal microbiota transplantation to restore the gut microbiota and improve patients' outcomes is being developed in the setting of allogeneic HCT, but also probably very soon in patients receiving autologous HCT or CAR T cells.

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The influence of drug prices, new availability of inexpensive generic imatinib, new approvals, and post-marketing research on the treatment of chronic myeloid leukaemia in the USA.

The role of third-generation TKIs as second-line therapy following front-line resistance to second-generation TKIs needs to be evaluated. New and mature data with TKI therapy in chronic myeloid leukaemia are producing observations that encourage continuous discussion of the optimal treatment recommendations and frameworks in chronic myeloid leukaemia.

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Leukemia

Extracorporeal photopheresis in acute and chronic steroid-refractory graft-versus-host disease: an evolving treatment landscape.

In this "Review" article we would like to offer strategies for improving treatment results in patients with steroid-refractory GvHD by combining ruxolitinib with extracorporeal photopheresis (ECP), a leukapheresis-based immunomodulatory treatment frequently applied in T-cell mediated immune disease including GvHD. Our article explores key published evidence supporting the clinical efficacy of both ruxolitinib and ECP in the treatment of GvHD and highlights their potentially complementary mechanisms of action.

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Miscellaneous

misc publications eg case reports, tools of the trade, images of the month, etc…

Am J Hematol

Drug-Induced Hypersensitivity Syndrome and Eosinophils in Skin Biopsy in a patient with Pancytopenia.

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Blood

An unusual myelofibrosis.

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Caulier A, Sankaran VG. Molecular and cellular mechanisms that regulate human erythropoiesis. Blood. 2022;139(16):2450-2459.

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Elsaid R, Meunier S, Burlen-Defranoux O, et al. A wave of bipotent T/ILC-restricted progenitors shapes the embryonic thymus microenvironment in a time-dependent manner. Blood. 2021;137(8):1024-1036.

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Freeman SD, Valk P. Transplant in older adults with AML: genomic wheat and chaff. Blood. 2022;139(24):3459-3461.

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Funk CR, Wang S, Chen KZ, et al. PI3Kd/ inhibition promotes human CART cell epigenetic and metabolic reprogramming to enhance antitumor cytotoxicity. Blood. 2022;139(4):523-537.

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Morphologic findings often provide guidance when immunophenotypic data overlap: a case of AML with cup-shaped nuclei.

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Steiner L. Helping GATA1 make complex decisions. Blood. 2022;139(24):3457-3459.

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Timing of allo-HCT in CMML.

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Blood Adv

Do sophisticated models give the full picture of allogeneic hematopoietic stem cell transplantation effect?

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Germline SNPs previously implicated as prognostic biomarkers do not associate with outcomes in intensively treated AML.

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Inaccuracies in assignment of patient race and ethnicity: implications for unrelated donor searches and healthcare delivery.

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Targeting FOLR1 in high-risk CBF2AT3-GLIS2 Pediatric AML with STRO-002 FOLR1-Antibody-Drug Conjugate.

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Vaccine-boosted convalescent plasma therapy for patients with immunosuppression and COVID-19.

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Lancet Haematol

A survey on the patient perspective on cure in multiple myeloma.

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Monika Asnani - addressing the unmet needs of sickle cell disease.

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Should patients with haemophilia receive gene therapy?

Pubmed   Journal   ReadQx 

The underrepresented majority.

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Venetoclax activity in a patient with central nervous system involvement by chronic lymphocytic leukaemia.

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Leukemia

Activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1.

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IgM-secreting diffuse large B-cell lymphoma: results of a multicentre clinicopathological and molecular study.

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Luspatercept mitigates bone loss driven by myelodysplastic neoplasms and estrogen-deficiency in mice.

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Organ dysfunction, thrombotic events and malignancies in patients with idiopathic multicentric castleman disease: a population-level US health claims analysis.

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

"Perioperative management of myeloproliferative neoplasms: a pan-Canadian physician survey and international expert opinion".

Pubmed   Journal   ReadQx 

A comment on: "Proton pump inhibition for secondary hemochromatosis in hereditary anemia: a phase III placebo-controlled randomized cross-over clinical trial".

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A reply to Moris et al.

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Blood

Hybrid immunity in immunocompromised patients with CLL after SARS-CoV-2 infection followed by booster mRNA vaccination.

Pubmed   Journal   ReadQx   PMC

Blood Cancer J

Hematopoietic differentiation at single-cell resolution in NPM1-mutated AML.

Pubmed   Journal   ReadQx   PMC

I-OPen: inferior outcomes of penta-refractory compared to penta-exposed multiple myeloma patients.

Pubmed   Journal   ReadQx   PMC

Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.

Pubmed   Journal   ReadQx   PMC

Lancet Haematol

Blueprint for greater security of immunoglobulins for patients in Canada.

Pubmed   Journal   ReadQx 

Prioritising health equity alongside donation safety - Authors' reply.

Pubmed   Journal   ReadQx 

Prioritising health equity alongside donation safety.

Pubmed   Journal   ReadQx 

Should unrelated haematopoietic progenitor cell donors be tested for CD36 in Japan?

Pubmed   Journal   ReadQx 

Leukemia

The WHO classification of haematolymphoid tumours: response to Swerdlow et al.

Pubmed   Journal   ReadQx